Hepatitis C virus (HCV) is one of the leading causes of liver cancer worldwide. Studies on HCV replication have been hampered by the lack of a convenient animal model or a reliable tissue culture system to propagate the virus. Investigators have focused on expression of HCV genes for functional and structural studies Most of the HCV non- structural proteins examined so far have been localized to the endoplasmic reticulum (ER). It is assumed therefore that expression of HCV NS4A/B precursor proteins results in the swelling of ER-like compartments and inhibits protein traffic between ER and Golgi apparatus. Thus, it is likely that HCV/NS4A/B o=precursor proteins inhibit cellular secretory pathway and modify intracellular compartments to form viral RNA replication complexes. In this proposal, the nature of the swollen intracellular compartments and their relationship to the HCV NS4A/B precursor proteins will be investigated. The ability of other HCV non-structural proteins (NS2/3/4A, NS4B/5A, NS4B/5A, NS4A and NS5B) to inhibit protein traffic will also be examined. Using MHC class I molecules, the specificity of this inhibition by HCV proteins will be tested. Similar studies will be done with homologous proteins of BVDV, a flavivirus that can be conveniently and safely be grown in tissue culture. Information gained from these studies will be useful in the selection of inhibitors or pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA095086-02
Application #
6623018
Study Section
Subcommittee G - Education (NCI)
Program Officer
Ojeifo, John O
Project Start
2002-07-01
Project End
2004-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$132,840
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Stone, Michelle; Jia, Shuaizheng; Heo, Won Do et al. (2007) Participation of rab5, an early endosome protein, in hepatitis C virus RNA replication machinery. J Virol 81:4551-63
Konan, Kouacou V; Giddings Jr, Thomas H; Ikeda, Masanori et al. (2003) Nonstructural protein precursor NS4A/B from hepatitis C virus alters function and ultrastructure of host secretory apparatus. J Virol 77:7843-55